Inorganic sorption materials tailored for 225Ra/225Ac and 225Ac/213Bi radionuclide generators for biomedical applications

Bussé Jakob

Promoter

Binnemans Koen, (KULeuven), koen.binnemans@chem.kuleuven.be

SCK•CEN Mentor

Van Hoecke Karen
karen.van.hoecke@sckcen.be
+32 14 33 82 01

SCK•CEN Co-mentor

Gysemans Mireille
mireille.gysemans@sckcen.be
+32 14 33 32 80

Expert group

Radiochemistry

PhD started

2017-10-01

Short project description

Biomedical applications of radionuclides, such as radiotherapy and medical imaging, require pure fractions of a broad range of radionuclides, which is mostly achieved by chromatographic column separation. Solid phases predominantly used in chromatographic separation, such as alumina or organic ion exchange resins (e.g. Dowex® AG-50W, Dowex® 1x8) and extraction resins (Triskem® TRU, RE, LN products) suffer from several drawbacks, e.g. limited shelf-life, low sorption capacity and radiolysis [1-3]. Alternatively, inorganic materials, such as amorphous activated carbon and titanium dioxide (titania), tailored for specific radionuclidic separations can potentially overcome those limitations. This project focuses on the development of innovative inorganic sorption materials for the production of 225Ra/225Ac and 225Ac/213Bi generators. Initially, the mother isotope, resp. 225Ra and 225Ac, is sorbed onto a solid material with high affinity for the mother isotope. Due to radioactive decay, the daughter isotope, resp. 225Ac and 213Bi, accumulates in the material and can be eluted at regular intervals. Hence, cationic separations of Ra2+ from Ac3+ and Ac3+ from Bi3+ are required. Both 225Ac and 213Bi are key isotopes of interest in nuclear medicine for targeted α-therapy [4,5].

This project focuses first on the development of functionalized activated carbon as sorption material. In order to diversify the sorption behaviour, both the nature of the activated carbon as the type of surface modification (e.g. sulphonic acid (R-SO3H) and phosphonic acid (R-PO3H2) derivatives) will be optimised. In case objectives cannot be obtained with this material, a backup material will be considered (functionalized titania).

This project will be performed in collaboration with VITO and KU Leuven, at which expertise in shaping and functionalization of the abovementioned materials is present [6].

Objective

The aim of this project is to develop strategies to manufacture functionalized sorption materials and test them for application in a new type of 225Ra/225Ac and 225Ac/213Bi generator. The target material has the following characteristics: (1) high separation factors (SFs) for the ion pairs (αRa/Ac and αAc/Bi), (2) high resistance against radiolysis, (3) high sorption capacity and (4) uniform spherical shape with narrow size distribution to allow optimal column packing.

The work flow is composed of synthesis of the functionalised material followed by a systematic evaluation of the abovementioned criteria, starting with the most essential one. This way, each new material will go through the following cycle of five stages: (1) synthesis (2) evaluation of separation chemistry (3) evaluation of radiation resistance (4) final shaping into uniform spheres and (5) test and validation of the generator. This flow chart is schematically presented in Figure 1.

 

file:///C:/Users/cmeeuwis/Downloads/1645.jpg

Figure 1 - Stages involved in production and evaluation of new inorganic sorption materials for radionuclidic generators for medical applications

  1. Synthesis and surface modification of sorption materials

The main selection criteria for the sorption material are dominated by the harsh experimental conditions, imposing a.o. a high radiation resistance and acid stability. By combining a tuned pore structure with specific surface modifications, a superior separation performance is targeted.

A first class of selected materials are activated carbons, which are widely recognised as sorbent materials due to the variety in pore structure and surface chemistry [7]. Its non-crystalline structure is indicative for a high radiation resistance. In literature, several approaches have been described to form a (meso)porous carbon (composite) material and to activate its surface, either by thermal, chemical or plasma treatment [8]. Depending on the source materials and on the conditions of the activation, a range of functional groups can be formed on the surface (either containing oxygen, nitrogen, phosphor or sulphur containing species) [9] . These surface groups can then be used as anchoring points for further chemical functionalisation. As such, the designed surface chemistry leads to improved separation performance, pH stability (low pKa) and radiation stability (aromatic functionality). For a first generation material, two activated carbon materials will be prepared with different properties and functionalized with two chemical groups (resulting thus in four different first generation materials).

A backup class of materials could be functionalized mesoporous TiO2, which have been applied in the selective sorption of actinides [10]. These materials demonstrate a superior hydrolytic resistance and radiation stability compared to a.o. polymer-based resins [11].

  1. Evaluation of separation chemistry with respect to Ra/Ac and Ac/Bi separation

Batch experiments will be performed to determine distribution coefficients (KD) for cations of interest between solid and aqueous phase as a function of the aqueous phase composition (pH, mineral acid type and concentration, salinity, concentration of other ions) and temperature will be performed. Initially, “cold” tests will be performed with Ba as simulant for Ra and La as simulant for Ac, followed by “hot” tests using Ra and Ac tracers. The final result will be the determination of SFs in function of the abovementioned parameters.

  1. Evaluation of radiation resistance

Suspensions of sorption materials that successfully passed the second stage, will be exposed to gamma radiation up to a dose of ca. 20 kJ/kg of sorption material in either the spent fuel or 60Co gamma irradiation facility at SCK•CEN. Since radiolytic damage to ion exchange resins is higher when exposed to gamma radiation compared to alpha radiation, no radiolysis studies using alpha irradiation will be performed [3]. Afterwards, batch experiments to evaluate SFs, SEM for particle morphology analysis, FT-IR spectroscopy for functional group analysis will allow to evaluate the radiation resistance of functionalized sorption materials. Only those materials that are sufficiently resistant will enter stage four of the cycle.

  1. Shaping of successful material into porous powder with uniform characteristics

Based on the separation performance and data of the radiation resistance, 1 or 2 materials will be selected to be shaped by controlled coagulation into spherical microspheres. The structural uniformity and spherical shape of the sorption material will be reflected in an improved column packing and elution characteristics [12]. In order to balance the mechanical properties and the porous architecture, different shaping approaches can be developed, either based on the use of inorganic binders or the carbonisation of polymeric templates. The porous architecture of the microspheres will be analysed by a combination of analytical tools including N2 sorption, Hg porosimetry and SEM.

Once shaped, the knowledge on the surface functionalisation of powders will be transferred to that of the microsphere.

  1. Test and validation of generator

After shaping, the selected materials are evaluated by column chromatography for the cold system under conditions based on the KD values determined in stage 2 for Ba, La and Bi. Finally, column hot chromatographic experiments with Ra, Ac and Bi will be performed to evaluate and optimize Ra/Ac and Ac/Bi separations, taking into account the presence of 209Pb, which is a daughter nuclide of the series.

Stages 1 and 4 will be performed at VITO, stages 2, 3, and 5 will be performed at SCK•CEN. All work will be done with strong interaction of the university promotor of KU Leuven.

References

1. L'Annunziata, M. F. Handbook of Radioactivity Analysis.  (Elsevier Science, 2012).

2. Dash, A. & Knapp, F. F. R. An overview of radioisotope separation technologies for development of W-188/Re-188 radionuclide generators providing Re-188 to meet future research and clinical demands. Rsc Advances 5, 39012-39036, doi:10.1039/c5ra03890a (2015).

3. Specht, S., Schütz, B. O. & Born, H. J. Development of a high-pressure ion-exchange system for rapid preparative separations of trans-uranium elements. Journal of Radioanalytical Chemistry 21, 167-176, doi:10.1007/BF02520859 (1974).

4. Apostolidis, C., Molinet, R., Rasmussen, G. & Morgenstern, A. Production of Ac-225 from Th-229 for targeted alpha therapy. Analytical Chemistry 77, 6288-6291, doi:10.1021/ac0580114 (2005).

5. Morgenstern, A., Bruchertseifer, F. & Apostolidis, C. Targeted alpha therapy with 213Bi. Current Radiopharmaceuticals 4, 295-305 (2011).

6. VITO, KULeuven & UGhent.  SIM-MARES project Get-A-Met: Groundbreaking Extraction technology for critical Metals and Metalloids from industrial wastewaters  (2016-2020).

7. Pyrzynska, K. Application of carbon sorbents for the concentration and separation of metal ions. Analytical Sciences 23, 631-637, doi:10.2116/analsci.23.631 (2007).

8. Enterría, M. & Figueiredo, J. L. Nanostructured mesoporous carbons: Tuning texture and surface chemistry. Carbon 108, 79-102, doi:10.1016/j.carbon.2016.06.108 (2016).

9. Rivera-Utrilla, J. et al. Activated carbon modifications to enhance its water treatment applications. An overview. Journal of Hazardous Materials 187, 1-23, doi:10.1016/j.jhazmat.2011.01.033 (2011).

10. Veliscek-Carolan, J., Jolliffe, K. A. & Hanley, T. L. Selective sorption of actinides by titania nanoparticles covalently functionalized with simple organic ligands. ACS Applied Materials and Interfaces 5, 11984-11994, doi:10.1021/am403727x (2013).

11. Chiarizia, R. & Horwitz, E. P. Radiolytic stability of some recently developed ion exchange and extraction chromatographic resins containing diphosphonic acid groups. Solvent Extraction and Ion Exchange 18, 109-132 (2000).

12. Roosen, J., Pype, J., Binnemans, K. & Mullens, S. Shaping of Alginate-Silica Hybrid Materials into Microspheres through Vibrating-Nozzle Technology and Their Use for the Recovery of Neodymium from Aqueous Solutions. Industrial & Engineering Chemistry Research 54, 12836-12846, doi:10.1021/acs.iecr.5b03494 (2015).